Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

Abstract

BackgroundSevere acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls.ResultsThe number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis.ConclusionsThis differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.

The replication of a mouse adapted SARS-CoV in a mouse cell line stably expressing the murine SARS-CoV receptor mACE2 efficiently induces the expression of proinflammatory cytokines

“…Using genomic analysis, it has been shown that gene expressions encoding proinflammatory cytokines are increased in DBT-mACE2 cells, compared to mock-infected cells. These results correlate with the data obtained in SARS patients (Cameron et al, 2007; Huang et al, 2005; Jiang et al, 2005; Reghunathan et al, 2005; Tang et al, 2005; Wong et al, 2003; Zhang et al, 2004) and in SARS-CoV-infected monkeys and mice (Baas et al, 2008; de Lang et al, 2007; Smits et al, 2010; Smits et al, 2011). In addition, it has been shown that SARS-CoV-MA15 infection induced a limited IFN-β production in DBT-mACE2 cells.…”

“…However, even with these viral strategies of defensive evasion and offensive antagonism of interferons, there are well-described host proinflammatory responses to in vivo SARS-CoV infections. Inflammatory mediators such as interleukin (IL)-1, −6, and −8, CXCL10/interferon-inducible protein (IP)-10, CCL2/monocyte chemoattractant protein (MCP)-1, CCL5/protein regulated and normal T expressed and secreted (RANTES), and CXCL9/monokine induced by interferon gamma (MIG) have been recognized in lungs of patients affected by SARS (Cameron et al, 2007; Huang et al, 2005; Jiang et al, 2005; Reghunathan et al, 2005; Tang et al, 2005; Wong et al, 2003; Zhang et al, 2004). Upregulation of genes mediating inflammation has also been described after infection with SARS-CoV in different animal models such as cynomolgus macaques and African green monkeys (de Lang et al, 2007; Smits et al, 2010; Smits et al, 2011) and mice (Baas et al, 2008).…”

Studying Lactoferrin N-Glycosylation

“…Oral administration of lactoferrin has been proposed to exert various beneficial health effects in humans and animals, including anti-cancer, anti-inflammatory, and anti-infective activities [9,10,11]. Lactoferrin is also used for the prevention of lipid oxidation and the improvement of microflora [12,13]. …”

Multi-omic network signatures of disease

“…Both histones and elongation factors have previously been associated with SARS-CoV infection (Reghunathan et al, 2005). …”